The overall objective of this proposed research is to develop polarization sensitive optical coherence tomography (PS-OCT) as a non-invasive optical device for the accurate and early clinical assessment of tooth demineralization and remineralization. The central hypothesis underlying this proposal is that the depth-resolved changes in the magnitude of light scattering of dental hard tissues at 1310-nm, that occur upon demineralization and remineralization, can be imaged and quantified in vivo using PS-OCT and that those changes can be correlated with the structural changes and relative mineral loss measured using polarized-light microscopy and microradiography. The overall objectives of this proposal will be achieved through the following specific aims: (1) To test the hypothesis that the lesion volume and reflectivity from that volume can be automatically assessed in simulated in vitro caries models and natural lesions on extracted teeth using a high speed PS-OCT scanning system; (2) To test the hypothesis that PS-OCT can be used to longitudinally monitor demineralization and the inhibition of demineralization by fluoride in an extended clinical study; (3) To test the hypothesis that PS-OCT can be used to detect changes in the structure and severity of existing lesions after exposure to a remineralization agent in vivo. These studies will further validate PS-OCT as a clinical tool for the accurate and early clinical assessment of tooth demineralization and remineralization. This is expected to lead to the clinical implementation of PS-OCT for the assessment and monitoring of the activity and severity of early carious lesions without the use of ionizing radiation, leading to an increased efficiency of caries clinical trials and a marked reduction in their scope and cost.